Contributed by Muhammad Omar Chohan MD1, Tausif Rehman MD1, Rafael Medina-Flores MD2, Carol Clericuzio MD3, Richard Heideman MD4, and Erich Marchand MD1
Departments of 1Neurosurgery, 2Pathology, 3Pediatric Genetics and 4Pediatric Hematology Oncology, University of New Mexico, Albuquerque, NM 87131-0001, USA.
A 16 month old female was admitted to the Pediatric Intensive Care Unit with fever, hypoxia, altered mental status, and seizures. Magnetic resonance imaging (MRI) of the brain (Figure 1) showed a single well circumscribed intraventricular mass which was isointense to cortex on T1-and T2-weighted images, and demonstrated mildly restricted diffusion consistent with dense cell packing. The mass measured 4x4x4 cm in the craniocaudal, AP and transverse dimensions. FLAIR imaging revealed mass effect secondary to the tumor causing trapping of the left temporal horn. There was additional, but mild right lateral ventricular dilatation and an 11 mm midline shift as measured at the level of the anterior portion of the third ventricle. Edema was seen along the corpus callosum, surrounding the mass extending into the left occipital lobe, temporal lobe, and parietal lobe. These signal characteristics were most suggestive of an intraventricular meningioma or a supratentorial primitive neuroectodermal tumor.
The patient subsequently had surgical resection of the mass with MRI Navigation guidance. Intraoperatively the mass had a thick capsule and a rubber like core. The entire tumor was removed without intraoperative complications. The patient was discharged home 4 days later and had done well since that time with no neurological deficits.
H&E stained sections showed a cellular tumor (Fig 2) with areas of geographical necrosis (Fig 3). Also observed were macronuclei and a relatively high mitotic rate (13 mitoses per 10 high power fields). Immunostains for Ki-67 showed a proliferation index estimated at 30-40% (Fig 4) and focal immunoreactivity for epithelial membrane antigen (EMA) (Figure 5). No cytokeratin or GFAP immunoreactivity was observed.
Due to the atypical radiological and pathological characteristics, a syndromic association was sought. This included a comprehensive NF2 mutation analysis on the pathological tissue. This analysis revealed two pathogenic mutations in the neurofibromatosis type 2 (NF2) gene; a 169C>T truncating mutation leading to a premature stop codon and a total NF2 gene deletion. Since the patient had no immediate family history of NF2, further genetic analysis was indicated to verify whether there was an NF2 germline mutation (NF2 Test 2). Singleton cases as this can reveal mosaicism in a constitutional blood study. Analysis of the patient's constitutional lymphocyte DNA revealed the same truncating NF2 mutation and thus the patient was diagnosed with NF2. The child's parents underwent extensive genetic counseling and were encouraged to undergo NF2 mutation analysis as both are in their early twenties and could have pre-symptomatic NF2.